Objective To provide suggestions for helping marketing authorization holders(MAHs)to develop an effective and compliant pharmacovigilance system.Methods The construction strategies of pharmacovigilance system of the m...Objective To provide suggestions for helping marketing authorization holders(MAHs)to develop an effective and compliant pharmacovigilance system.Methods The construction strategies of pharmacovigilance system of the multinational pharmaceutical companies were analyzed based on the requirements of regulations and laws.Results and Conclusion There are some gaps between local and multinational pharmaceutical companies in the construction of pharmacovigilance system.We can learn from the experience of multinational pharmaceutical companies to improve the pharmacovigilance system,which includes building a sound pharmacovigilance organizational structure,establishing a series of operational system files and cultivating professional talents.MAHs of China should improve the structure of enterprise pharmacovigilance system.Besides,members of Drug Safety Committee should be department managers with higher position so that they can fulfil the responsibilities of risk assessment.If MAHs possess a large variety and quantity of products,a Drug Safety Committee should be established to ensure the timely discovery of risks.In addition,MAHs should pay attention to the implementation of related regulations and laws on pharmacovigilance and establish compliant,effective and operatable files combing with the actual operation of pharmacovigilance system.Finally,MAHs should introduce and train pharmacovigilance talents,and hire pharmacovigilance experts as consultants to solve the problem of talent shortage.展开更多
Constituting the reasonable control models of the wrinkle limit blank holder forces is the sticking point of the processes of the deep drawing with variable blank-holder forces, especially in the square-box forming. T...Constituting the reasonable control models of the wrinkle limit blank holder forces is the sticking point of the processes of the deep drawing with variable blank-holder forces, especially in the square-box forming. To begin with, a mode of segmenting flange of the square-box into eight zones is put forward according to the fact that the uniformity of flange deforming can be improved by control-ling segment blank-holders. Considering the integral influence of shear stress, a new concept, strain relaxation factor is defined. Hereby, the law of distribution of stress and stain in the deforming flange of square-box is achieved. Then based on these mechanical analysis models and the energy principle, the wrinkling flexivity functions of the straight flange and the circle flange are given, and the corresponding formulae of wrinkling limit blank-holder force in these two situations are also educed. In these processes, ply-anisotropy, strain hardening, thickness and friction are considered. In the end, a calculating example is designed to validate the rationality of the formulae of wrinkling limit blank-holder force, at the same time, the influences of the ply-anisotropy exponent and the strain hardening exponent on the wrinkle limit blank holder forces are also analyzed.展开更多
The aim of this study was to provide insights into the current status and primary methodologies employed by marketing authorization holders(MAHs)for signal detection.These insights are intended to offer valuable refer...The aim of this study was to provide insights into the current status and primary methodologies employed by marketing authorization holders(MAHs)for signal detection.These insights are intended to offer valuable references for regulatory authorities in shaping pertinent regulatory policies.We conducted purposive sampling interviews with personnel responsible for pharmacovigilance(PV)within MAHs,in accordance with“Good Pharmacovigilance Practice(GVP)”.The interviews covered six predefined topics with open-ended discussions,including signal collection,signal detection,signal evaluation,clustered signal detection,and current challenges and issues.A total of 26 MAHs were interviewed,comprising 14 foreign-owned and 12 domestic enterprises.Foreign-owned enterprises,along with some local innovative pharmaceutical companies,utilized Oracle’s Argus and Empirica for adverse drug reaction information storage and computer-aided quantitative signal detection,respectively.The majority of domestic enterprises used the Taimei system for data storage and qualitative analysis,although a few employed other systems.Foreign-owned MAHs had comprehensive drug vigilance systems,aligning with established standards such as those of the European Union and the United States.Domestic innovative MAHs had more comprehensive drug vigilance systems compared to traditional domestic MAHs.Their signal detection approaches drew inspiration from the practices of foreign MAHs.This work synthesized findings related to the state of PV practices within these MAHs,shedding light on the challenges,achievements,and potential pathways for improvement.展开更多
Objective To ensure the quality and safety of drugs in the whole cycle of pharmaceutical commissioned production under the drug marketing authorization holder(MAH)system,and to establish a perfect quality management s...Objective To ensure the quality and safety of drugs in the whole cycle of pharmaceutical commissioned production under the drug marketing authorization holder(MAH)system,and to establish a perfect quality management system for it.Methods Literature review was used to study the factors that influenced the quality management system of pharmaceutical commissioned production because the implementation of MAH system in China was late,and the experience accumulated by pharmaceutical industry was not enough.Results and Conclusion Based on the MAH system,it is of great significance to establish the quality management system for pharmaceutical commissioned production.展开更多
In the article,we provide a sharp lower bound for the weighted Lehmer mean of the complete p-elliptic integrals of the first and second kinds,which is the extension of the previous results for complete p-elliptic inte...In the article,we provide a sharp lower bound for the weighted Lehmer mean of the complete p-elliptic integrals of the first and second kinds,which is the extension of the previous results for complete p-elliptic integrals.展开更多
Nine representatives of the National March 8 Redbanner Holders of 2018 shared their experiences with 51 female overseas students during a meeting at China Women's University (CWU), in Beijing, on March 13.
THE convention of traditional Chinese medicine requires passing on what has been accumulated during generations past to the family’s male descendants instead of females, because women enter into other families after ...THE convention of traditional Chinese medicine requires passing on what has been accumulated during generations past to the family’s male descendants instead of females, because women enter into other families after marriage. If a family has no male descendants, the convention requires展开更多
In this short paper,we remove the restrictionγ∈(1,3]that was used in the paper"The rate of convergence of the viscosity method for a nonlinear hyperbolic system"(Nonlinear Analysis,1999,38:435-445)and obta...In this short paper,we remove the restrictionγ∈(1,3]that was used in the paper"The rate of convergence of the viscosity method for a nonlinear hyperbolic system"(Nonlinear Analysis,1999,38:435-445)and obtain a global Holder continuous solution and the convergent rate of the viscosity method for the Cauchy problem of the variant nonisentropic system of polytropic gas for any adiabatic exponentγ>1.展开更多
In this paper,I consider the Hölder continuity of the Lyapunov exponent for a quasi-periodic Szegö cocycle with weak Liouville frequency.I extend the existing results about the regularity of the Lyapunov exp...In this paper,I consider the Hölder continuity of the Lyapunov exponent for a quasi-periodic Szegö cocycle with weak Liouville frequency.I extend the existing results about the regularity of the Lyapunov exponent from the Schrödinger cocycle in[24]to a Szegö cocycle.展开更多
Clifford analysis is an important branch of modern analysis;it has a very important theoretical significance and application value,and its conclusions can be applied to the Maxwell equation,Yang-Mill field theory,quan...Clifford analysis is an important branch of modern analysis;it has a very important theoretical significance and application value,and its conclusions can be applied to the Maxwell equation,Yang-Mill field theory,quantum mechanics and value problems.In this paper,we first give the definition of a quasi-Cauchy type integral in complex Clifford analysis,and get the Plemelj formula for it.Second,we discuss the H?lder continuity for the Cauchy-type integral operators with values in a complex Clifford algebra.Finally,we prove the existence of solutions for a class of linear boundary value problems and give the integral representation for the solution.展开更多
Blank holder force(BHF)is a crucial parameter in deep drawing,having close relation with the forming quality of sheet metal.However,there are different BHFs maintaining the best forming effect in different stages of d...Blank holder force(BHF)is a crucial parameter in deep drawing,having close relation with the forming quality of sheet metal.However,there are different BHFs maintaining the best forming effect in different stages of deep drawing.The variable blank holder force(VBHF)varying with the drawing stage can overcome this problem at an extent.The optimization of VBHF is to determine the optimal BHF in every deep drawing stage.In this paper,a new heuristic optimization algorithm named Jaya is introduced to solve the optimization efficiently.An improved“Quasi-oppositional”strategy is added to Jaya algorithm for improving population diversity.Meanwhile,an innovated stop criterion is added for better convergence.Firstly,the quality evaluation criteria for wrinkling and tearing are built.Secondly,the Kriging models are developed to approximate and quantify the relation between VBHF and forming defects under random sampling.Finally,the optimization models are established and solved by the improved QO-Jaya algorithm.A VBHF optimization example of component with complicated shape and thin wall is studied to prove the effectiveness of the improved Jaya algorithm.The optimization results are compared with that obtained by other algorithms based on the TOPSIS method.展开更多
基金Integration Application Status and Problems Investigation of ICH Q8,Q9,Q10 across the Product Life Cycle(No.20210605).
文摘Objective To provide suggestions for helping marketing authorization holders(MAHs)to develop an effective and compliant pharmacovigilance system.Methods The construction strategies of pharmacovigilance system of the multinational pharmaceutical companies were analyzed based on the requirements of regulations and laws.Results and Conclusion There are some gaps between local and multinational pharmaceutical companies in the construction of pharmacovigilance system.We can learn from the experience of multinational pharmaceutical companies to improve the pharmacovigilance system,which includes building a sound pharmacovigilance organizational structure,establishing a series of operational system files and cultivating professional talents.MAHs of China should improve the structure of enterprise pharmacovigilance system.Besides,members of Drug Safety Committee should be department managers with higher position so that they can fulfil the responsibilities of risk assessment.If MAHs possess a large variety and quantity of products,a Drug Safety Committee should be established to ensure the timely discovery of risks.In addition,MAHs should pay attention to the implementation of related regulations and laws on pharmacovigilance and establish compliant,effective and operatable files combing with the actual operation of pharmacovigilance system.Finally,MAHs should introduce and train pharmacovigilance talents,and hire pharmacovigilance experts as consultants to solve the problem of talent shortage.
文摘Constituting the reasonable control models of the wrinkle limit blank holder forces is the sticking point of the processes of the deep drawing with variable blank-holder forces, especially in the square-box forming. To begin with, a mode of segmenting flange of the square-box into eight zones is put forward according to the fact that the uniformity of flange deforming can be improved by control-ling segment blank-holders. Considering the integral influence of shear stress, a new concept, strain relaxation factor is defined. Hereby, the law of distribution of stress and stain in the deforming flange of square-box is achieved. Then based on these mechanical analysis models and the energy principle, the wrinkling flexivity functions of the straight flange and the circle flange are given, and the corresponding formulae of wrinkling limit blank-holder force in these two situations are also educed. In these processes, ply-anisotropy, strain hardening, thickness and friction are considered. In the end, a calculating example is designed to validate the rationality of the formulae of wrinkling limit blank-holder force, at the same time, the influences of the ply-anisotropy exponent and the strain hardening exponent on the wrinkle limit blank holder forces are also analyzed.
基金China National Key Research and Development Program(Grant No.2020YFC2009000 and 2020YFC2009001)National High Level Hospital Clinical Research Funding(Grant No.BJ-2023-200)the project funding from the Drug Evaluation Center of the National Medical Products Administration(Grant No.CDRW20214001).
文摘The aim of this study was to provide insights into the current status and primary methodologies employed by marketing authorization holders(MAHs)for signal detection.These insights are intended to offer valuable references for regulatory authorities in shaping pertinent regulatory policies.We conducted purposive sampling interviews with personnel responsible for pharmacovigilance(PV)within MAHs,in accordance with“Good Pharmacovigilance Practice(GVP)”.The interviews covered six predefined topics with open-ended discussions,including signal collection,signal detection,signal evaluation,clustered signal detection,and current challenges and issues.A total of 26 MAHs were interviewed,comprising 14 foreign-owned and 12 domestic enterprises.Foreign-owned enterprises,along with some local innovative pharmaceutical companies,utilized Oracle’s Argus and Empirica for adverse drug reaction information storage and computer-aided quantitative signal detection,respectively.The majority of domestic enterprises used the Taimei system for data storage and qualitative analysis,although a few employed other systems.Foreign-owned MAHs had comprehensive drug vigilance systems,aligning with established standards such as those of the European Union and the United States.Domestic innovative MAHs had more comprehensive drug vigilance systems compared to traditional domestic MAHs.Their signal detection approaches drew inspiration from the practices of foreign MAHs.This work synthesized findings related to the state of PV practices within these MAHs,shedding light on the challenges,achievements,and potential pathways for improvement.
文摘Objective To ensure the quality and safety of drugs in the whole cycle of pharmaceutical commissioned production under the drug marketing authorization holder(MAH)system,and to establish a perfect quality management system for it.Methods Literature review was used to study the factors that influenced the quality management system of pharmaceutical commissioned production because the implementation of MAH system in China was late,and the experience accumulated by pharmaceutical industry was not enough.Results and Conclusion Based on the MAH system,it is of great significance to establish the quality management system for pharmaceutical commissioned production.
基金Supported by the National Natural Science Foundation of China(11971142)the Natural Science Foundation of Zhejiang Province(LY19A010012)the key Scientific Research Projects of Hunan Provincial Department of Education in 2021(21A0526)。
文摘In the article,we provide a sharp lower bound for the weighted Lehmer mean of the complete p-elliptic integrals of the first and second kinds,which is the extension of the previous results for complete p-elliptic integrals.
文摘Nine representatives of the National March 8 Redbanner Holders of 2018 shared their experiences with 51 female overseas students during a meeting at China Women's University (CWU), in Beijing, on March 13.
文摘THE convention of traditional Chinese medicine requires passing on what has been accumulated during generations past to the family’s male descendants instead of females, because women enter into other families after marriage. If a family has no male descendants, the convention requires
基金supported by the National Natural Science Foundation of China(12071409)。
文摘In this short paper,we remove the restrictionγ∈(1,3]that was used in the paper"The rate of convergence of the viscosity method for a nonlinear hyperbolic system"(Nonlinear Analysis,1999,38:435-445)and obtain a global Holder continuous solution and the convergent rate of the viscosity method for the Cauchy problem of the variant nonisentropic system of polytropic gas for any adiabatic exponentγ>1.
文摘In this paper,I consider the Hölder continuity of the Lyapunov exponent for a quasi-periodic Szegö cocycle with weak Liouville frequency.I extend the existing results about the regularity of the Lyapunov exponent from the Schrödinger cocycle in[24]to a Szegö cocycle.
基金supported by the NSF of Hebei Province(A2022208007)the NSF of China(11571089,11871191)the NSF of Henan Province(222300420397)。
文摘Clifford analysis is an important branch of modern analysis;it has a very important theoretical significance and application value,and its conclusions can be applied to the Maxwell equation,Yang-Mill field theory,quantum mechanics and value problems.In this paper,we first give the definition of a quasi-Cauchy type integral in complex Clifford analysis,and get the Plemelj formula for it.Second,we discuss the H?lder continuity for the Cauchy-type integral operators with values in a complex Clifford algebra.Finally,we prove the existence of solutions for a class of linear boundary value problems and give the integral representation for the solution.
基金Supported by National Key Research and Development Program of China(Grant No.2022YFB3304200)National Natural Science Foundation of China(Grant No.52075479)Taizhou Municipal Science and Technology Project of China(Grant No.1801gy23).
文摘Blank holder force(BHF)is a crucial parameter in deep drawing,having close relation with the forming quality of sheet metal.However,there are different BHFs maintaining the best forming effect in different stages of deep drawing.The variable blank holder force(VBHF)varying with the drawing stage can overcome this problem at an extent.The optimization of VBHF is to determine the optimal BHF in every deep drawing stage.In this paper,a new heuristic optimization algorithm named Jaya is introduced to solve the optimization efficiently.An improved“Quasi-oppositional”strategy is added to Jaya algorithm for improving population diversity.Meanwhile,an innovated stop criterion is added for better convergence.Firstly,the quality evaluation criteria for wrinkling and tearing are built.Secondly,the Kriging models are developed to approximate and quantify the relation between VBHF and forming defects under random sampling.Finally,the optimization models are established and solved by the improved QO-Jaya algorithm.A VBHF optimization example of component with complicated shape and thin wall is studied to prove the effectiveness of the improved Jaya algorithm.The optimization results are compared with that obtained by other algorithms based on the TOPSIS method.
